Oral Presentation Australasian RNA Biology and Biotechnology Association 2026 Conference

Splice and Tell: Dissecting QKI-Regulated Alternative Splicing Networks in Prostate Cancer (144969)

Zoe K Price 1 , Yesha Ramani 1 , Jasleen Rajpal 1 , Josefanny Josefanny 1 , Helen M Palethorpe 1 , Daniel P Neumann 1 , Caroline A Chambers 1 , Katherine A Pillman 1 , Julie Bracken 1 , Kate Dredge 1 , Andrew G Bert 1 , Cameron P Bracken 1 , Luke A Selth 2 , Gregory J Goodall 1 , Brett G Hollier 3 , Philip A Gregory 1
  1. Centre for Cancer Biology, Adelaide University, Adelaide, SA, Australia
  2. Flinders Health and Medical Research Institute, Flinders University, Adelaide
  3. Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre, Queensland University of Technology, Brisbane, QLD

Androgen deprivation therapy (ADT) serves as a primary treatment in prostate cancer, however patients invariably develop resistance, progressing to incurable castration-resistant prostate cancer (CRPC). Androgen blockade triggers an adaptive response, promoting prostate tissue differentiation and fostering tumour cell plasticity; with features resembling epithelial-mesenchymal transition (EMT). Tumour cells with these properties are highly metastatic and resistant to ADT.

We have identified RNA binding protein Quaking (QKI) as a novel regulator of tumour cell plasticity in prostate cancer. In clinical prostate cancer samples, QKI expression increased following ADT and was further elevated in high-grade and CRPC clinical samples. To characterise the function of QKI in prostate cancer, QKI levels were manipulated in ADT sensitive and resistant cell lines.

QKI KO caused significant morphological changes and reduced cell migration and invasion of ADT resistant cells. RNA sequencing and CLIP-seq revealed broad changes in QKI regulated alternative splicing events. Selected events which displayed clinical relevance were modulated using RNA targeting CRISPR dCasRx followed by functional assays.  As an example, suppression of exon 3 inclusion of NFYA significantly reduced cell migration.

Our research highlights the broad landscape of splicing events regulated by QKI and demonstrates the potential to characterise functions of individual splice events during prostate cancer progression.